June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Comparison of Effects Upon Intraocular Inflammation and Murine Aqueous Humor Dynamics Parameters of Intravitreal Injection of Ad5.CMV.hTGFβ2C226/228S and LV.hTGFβ2C226/228S
Author Affiliations & Notes
  • J Cameron Millar
    Pharmacology & Neuroscience, and North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Shruti V Patil
    Pharmacology & Neuroscience, and North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Gulab Zode
    Pharmacology & Neuroscience, and North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   J Cameron Millar Adtech Pharma Inc., Code C (Consultant/Contractor), Santen Pharmaceuticals, Code C (Consultant/Contractor), CRSPRTX, Code C (Consultant/Contractor); Shruti Patil None; Gulab Zode Santen Pharmaceuticals, Code C (Consultant/Contractor)
  • Footnotes
    Support  R01 EY026177-06A1
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3478. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J Cameron Millar, Shruti V Patil, Gulab Zode; Comparison of Effects Upon Intraocular Inflammation and Murine Aqueous Humor Dynamics Parameters of Intravitreal Injection of Ad5.CMV.hTGFβ2C226/228S and LV.hTGFβ2C226/228S. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3478.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Intravitreal (IVT) injection in mice of adenoviral 5 (Ad5) vector carrying the hTGFβ2C226/228S gene leads to elevation of intraocular pressure (IOP) by recapitulating changes to the trabecular meshwork seen in primary open-angle glaucoma (POAG). But mild to moderate inflammation often results. Lentiviral (LV) vectors can achieve similar gene transduction but without causing inflammation. Here we compared, in mice, the effects of IVT injection of Ad5.CMV.hTGFβ2C226/228S with LV.CMV.hTGFβ2C226/228S on IOP elevation and other parameters of aqueous humor dynamics (AHD), specifically: aqueous humor flow rate (Fin), total aqueous outflow facility (Ctot), uveoscleral outflow rate (Fu), and episcleral venous pressure (EVP).

Methods : C57BL/6J mice (♀, 3-6 months, 20-30g) were utilized. Conscious baseline (BL) IOP measurements (TonoLab rebound tonometer) and ophthalmoscopic examinations were made in restrained animals. Animals were then divided into 2 cohorts (N=5/cohort), anesthetized with inhalation of isoflurane (2.5%) and O2(g) (0.8L/min), and given a single IVT injection (2µL) in one eye of a suspension of either: Ad5.CMV.hTGFβ2C226/228S (2×107pfu) or LV.CMV.hTGFβ2C226/228S (2×106pfu). Contralateral eyes were injected (2μL) respectively with Ad5.CMV.Null or LV.CMV.Null. IOP measurements and ophthalmoscopic observations were made OU once per week commencing 1 week following injection. When IOP was elevated, animals were anesthetized (ketamine (100mg/kg)/xylazine (10mg/kg)) and AHD parameters were determined (constant flow infusion).

Results : Ad5.CMV.hTGFβ2C226/228S injected eyes exhibited a mild to moderate tendency towards iridial hyperemia and lenticular cataract. A similar but less severe trend was seen in Ad5.Null-injected eyes. No such trend was seen in any LV-injected eyes. Ad5.Null or LV.Null-injected eyes showed no significant change in IOP from BL. IOP and AHD parameters are shown in the Table (below).

Conclusions : Both Ad5 and LV vectors are capable of generating an elevated IOP model in mice. However, while the Ad5 vector promotes intraocular inflammation, the LV vector does not. The LV vector takes a significantly longer time to generate its effects, and the IOP elevation is greater (73% over BL for LV @7 weeks vs. 48% over BL for Ad5 @2 weeks). Both vectors promote an increase in EVP.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×